Alleviative effect of microRNA-497 on diabetic neuropathic pain in rats in relation to decreased USP15,Cell Biology and Toxicology

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Alleviative effect of microRNA-497 on diabetic neuropathic pain in rats in relation to decreased USP15
Cell Biology and Toxicology ( IF 5.3 ) Pub Date : 2022-04-27 , DOI: 10.1007/s10565-022-09702-8
Tonghui Zhang ₁ , Ling Wang ₂ , Ling Chen ₃

Affiliation

The current study tries to discuss the functional role of microRNA-497 (miR-497) in diabetic neuropathic pain (DNP) and the related downstream mechanism. Bioinformatics analysis was implemented for the identification of differentially expressed miRNAs and genes. DNP was simulated in rats through intraperitoneal injection of streptozotocin. The expression patterns of miR-497, USP15, NRF2, and G6PD were then determined. The binding of miR-497 and USP15 was confirmed. Using gain- and loss-of-function assays, we analyzed the critical role of miR-497-mediated USP15 in DNP through the NRF2/G6PD axis. Downregulated miR-497 and elevated USP15 were observed in the dorsal root ganglion neurons isolated from spinal cord tissues of STZ-induced DNP rats. miR-497 could alleviate DNP, which was associated with suppression of USP15, a confirmed target of miR-497. USP15 enhanced the degradation and ubiquitination of NRF2 and induced G6PD expression, leading to the progression of DNP. We highlighted the crucial role of miR-497-mediated USP15 in DNP through the NRF2/G6PD axis.

Graphical abstract

1. miR-497 is downregulated in DRG neurons from spinal cord tissues of STZ-induced DNP rats.

2. miR-497 inhibits the expression of USP15, thereby alleviating STZ-induced DNP in rats.

3. USP15 promotes ubiquitination and degradation of NRF2, reducing the expression of G6PD.

4. miR-497 alleviates STZ-induced DNP in rats by regulating the USP15/NRF2/G6PD axis.

中文翻译：

microRNA-497 对大鼠糖尿病神经性疼痛的缓解作用与 USP15 降低有关

本研究试图探讨微小RNA-497（miR-497）在糖尿病神经病理性疼痛（DNP）中的功能作用及其相关下游机制。采用生物信息学分析来鉴定差异表达的 miRNA 和基因。通过腹腔注射链脲佐菌素在大鼠体内模拟 DNP。然后确定 miR-497、USP15、NRF2 和 G6PD 的表达模式。证实了 miR-497 和 USP15 的结合。使用功能获得和丧失分析，我们通过 NRF2/G6PD 轴分析了 miR-497 介导的 USP15 在 DNP 中的关键作用。在从 STZ 诱导的 DNP 大鼠脊髓组织中分离的背根神经节神经元中观察到 miR-497 下调和 USP15 升高。miR-497 可以减轻 DNP，这与抑制 USP15（miR-497 的已确认靶点）有关。USP15 增强了 NRF2 的降解和泛素化，并诱导 G6PD 表达，导致 DNP 的进展。我们强调了 miR-497 介导的 USP15 通过 NRF2/G6PD 轴在 DNP 中的关键作用。